USING NONSTEROIDAL
ANTIINFLAMMATORY DRUGS IN VOLUME- DEPLETED CHILDREN CAN PRECIPITATE ACUTE RENAL FAILURE
Submitted by John Cheri Mathews
Cheri Mathews John, Vivek Saroha, Caroline Jones Royal Liverpool Children’s Hospital, Liverpool,
United Kingdom
INTRODUCTION: Nonsteroidal antiinflammatory drugs (NSAIDs) are ever increasing in popularity in hos- pital medicine and general practice and are readily avail- able over-the-counter.
OBJECTIVE:Our goal was to illustrate the need to be aware of the effect of NSAIDs on dehydrated patients.
PATHOGENESIS:The risk of renal toxicity is increased in situations in which there is a stimulation of the renin- angiotensin system such as volume depletion. In these conditions, circulating vasoconstrictors are released, maintaining vascular resistance and blood pressure at the potential expense of regional organ blood flow. To maintain renal blood flow, counter-regulatory renal prostaglandins are released that counteract vasoconstric- tors and normalize renal blood flow. NSAIDs blunt this counter-regulatory response and intensify the renal va- soconstriction, which leads to acute renal failure. In Table 1 we report 4 children with mild dehydration who developed acute renal failure after the use of therapeutic doses of NSAIDs in a children’s hospital.
TABLE 1. Acute Renal Failure in 4 Children After Use of NSAIDs
Patient No.
1 2 3 4
Age, y 13 7 14 13
Gender Male Male Male Female
Underlying pathology Craniopharyngioma diabetes insipidus
Juvenile idiopathic arthritis; fasted for surgery Juvenile idiopathic arthritis with vomiting Relapse of Crohn disease
NSAID Diclofenac sodium Indomethacin diclofenac sodium
Diclofenac sodium Diclofenac sodium Highest urea level,
mmol urea/L
10.7 12.9 10.7 22
Highest creatinine level,
mol/L
226 146 376 629
Normalization, d 5 3 3 Permanent
impairment
CONCLUSIONS:We recommend that NSAIDs should be avoided in children with actual or potential intravas- cular volume depletion. Although we have not proven cause and effect, additional research is needed to define the true risk of the potential renal complications of using NSAIDs in patients who are at risk of dehydration.
NOTE: The cases of the 4 children described in this report have been published elsewhere (John CM, Shukla R, Jones CA. Using NSAID in volume depleted
children can precipitate acute renal failure. Arch Dis Child.2007;92:524 –526).
ROLES OF SCAP (STEROL REGULATORY ELEMENT–BINDING PROTEIN CLEAVAGE- ACTIVATING PROTEIN) IN THE MECHANISM FOR MESANGIAL FOAM-CELL FORMATION UNDER INFLAMMATORY STRESS
Submitted by Qiu Li Qiu Lia, Xiong Zhong Ruanb
aDivision of Nephrology and Immunology, Affiliated Children’s Hospital, Chongqing Medical University, Chongqing, China;bCentre for Nephrology, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom
INTRODUCTION:Our previous studies have demon- strated that lipid abnormalities play a significant role in glomerulosclerosis. Inflammatory cytokines promote lipid accumulation in human mesangial cells (HMCLs) by disrupting low-density lipoprotein receptor (LDLr) feedback regulation. The sterol regulatory element– binding protein (SREBP) cleavage-activating protein (SCAP) carries SREBP from endoplasmic reticulum (ER) to Golgi, where it is known to cleave SREBP, thereby enhancing LDLr gene expression and cholesterol uptake when cells need cholesterol.
OBJECTIVE:We aimed to investigate whether inflam- matory mediators interfere with SCAP translocation and its biological consequence.
METHODS:HMCLs were used in all experiments. Total cellular RNA was isolated from these cells for detecting LDLr, SREBP-2, and SCAP messenger RNA levels with real-time quantitative polymerase chain reaction. LDLr protein expression was measured by Western blot. Translocation of the SCAP-SREBP complex from the ER to Golgi was investigated by confocal microscopy.
RESULTS:In the absence of exposure to interleukin 1, a high concentration of LDL retained SCAP in the ER, a low LDLr promoter activity, messenger RNA synthesis, and protein expression were found, respectively. How- ever, exposure to interleukin 1caused overexpression of SCAP and enhanced its translocation from the ER to Golgi. This disrupted normal feedback regulation and resulted in inappropriately increased LDL uptake with transformation of HMCLs into foam cells. Overexpres- sion of SCAP in HMCLs resulted in an increased trans- location of SCAP from the ER to Golgi, and high con- centrations of LDL were unable to suppress SREBP-2 and LDLr gene expression.
CONCLUSIONS:These data suggest that inflammatory mediators promote abnormal translocation of SCAP from the ER to Golgi and play an important role in lipid accumulation in HMCLs.
NEITHER CLINICAL NOR BIOLOGICAL DATA CAN PREDICT RENAL INVOLVEMENT IN INFANTS WITH FEBRILE URINARY
TRACT INFECTION
Submitted by Nikoleta Printza
Nikoleta Printzaa, Fotios Papachristoua, Kaliopi Piretzia,
Chrissa Gogaa, Georgios Arsosb
aFirst Pediatric Department andbDepartment of Nuclear Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
INTRODUCTION: 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy is accepted as the gold standard in the diagnosis of acute pyelonephritis.
OBJECTIVE: In an attempt to reduce the number of investigations after urinary tract infections (UTIs), with this prospective study we aimed to evaluate the diagnos- tic value of acute-phase reactants in identifying renal involvement in infants with febrile UTI.
METHODS: Fifty-four infants (36 male, 18 female) aged 1 to 12 months were studied. For all infants, clinical findings such as duration and height of fever before antibiotic administration and laboratory parameters such as leukocytosis (white blood cell count of⬎15.000/
L), elevated erythrocyte sedimentation rate (ESR) (⬎20 mm/hour), and high levels of C-reactive protein (⬎10 mg/mL) were compared with the results of the DMSA scan obtained within 72 hours after referral.
RESULTS: Regarding microbial agents, Escherichia coli was identified in 42 (78%) of the 54 infants, and 16 (29.5%) of the 54 of infants were febrile for ⬎2 days before diagnosis of UTI. Leukocytosis, elevated ESR, and high levels of C-reactive protein were present in 14 (26%), 41 (76%), and 38 (70%) infants, respectively. Acute-phase DMSA showed renal involvement in 10 (18.5%) infants. Vesicoureteral reflux was found in 16 (29.5%) infants. Gender, duration of fever before anti- biotic administration, leukocytosis, elevated ESR, and high levels of C-reactive protein were not related to the severity of renal damage, as shown by DMSA. Only fever of ⬎39°C was slightly correlated with an abnormal DMSA scan result (r⫽0.3;P⫽.032).
CONCLUSIONS: Acute-phase DMSA scintigraphy re- mains superior to clinical and laboratory data for pre- dicting renal involvement in infants with febrile UTIs.
IMMUNE FINDINGS IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME: COULD THEY PREDICT THE RESPONSE TO STEROID THERAPY?
Submitted by Nikoleta Printza
Nikoleta Printza, Fotios Papachristou, Vassiliki Tzimouli, Anna Taparkou, Floredia Kanakoudi- Tsakalidou
First Pediatric Department, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece INTRODUCTION:Nephrotic syndrome (NS) is thought to be associated with primary immune disturbances.
OBJECTIVE: The aim of our study was to investigate prospectively the immune disturbances in steroid-sensi- tive (SS) and steroid-resistant (SR) NS and identify whether these immune disturbances may predict the response to steroid therapy.
METHODS:Thirty children with SS NS and 7 children with SR NS (aged 2 to 14 years) were studied. To eval- uate the possible relationship between immune distur- bances and response to treatment, patients were evalu- ated during different disease stages. Data were compared with those obtained from 25 age-matched controls. The following parameters were assessed: basic B- and T-cell populations, percentages of CD23⫹, CD3⫹/CD69⫹/inter- feron ␥⫹ (IFN-␥⫹) cells, and CD3⫹/CD69⫹/interleukin 4⫹(IL-4⫹) T cells, and serum levels of IL-13 and IL-18.
RESULTS:In patients with SS NS percentages of CD23⫹ and CD19⫹B cells, CD3⫹/CD69⫹/IL-4⫹T cells and se- rum levels of IL-13, IL-18 were significantly higher in the active stage compared with the remission stage on steroids, remission off steroids, and controls (P ⬍.05). On the contrary, percentages of CD3⫹/CD69⫹/IFN-␥⫹T cells were significantly decreased (P⬍.05). In patients with SR NS, percentages of CD23⫹B cells, CD3⫹/CD69⫹/ IL-4⫹T cells, and serum levels of IL-13 and IL-18 pre- sented no significant difference between active stage and partial remission. Percentages of CD19⫹ B cells and CD3⫹/CD69⫹/IFN-␥⫹ T cells were elevated in active stage compared with remission stage of patients with SR NS and in controls (P⬍.05).
CONCLUSIONS: These findings suggest that when a type-2 immune response is found in the active stage of NS, one could predict a good response to steroid therapy.
RENAL INVOLVEMENT IN CHILDREN WITH GLYCOGEN-STORAGE DISEASE
Submitted by Hesham Safouh
Hesham Safouha, Rokayya Elsayyeda, Samah
Mansoura, Gamal Tahab, Mortada Elshabrawya, Hanaa
Elkaraksya
aDepartment of Pediatrics, Cairo University, Cairo, Egypt; bDepartment of Pediatrics, Beni Sweif University, Beni Sweif, Egypt
INTRODUCTION: Long-term complications of glyco- gen-storage diseases (GSDs) include delayed puberty, hepatic adenomata, and renal disease.
OBJECTIVE:In this study, our aim was to detect renal involvement in children with GSD and to determine the most accurate laboratory test to be the gold standard for early detection of this renal dysfunction.
METHODS:Twenty-seven children known to have GSD were included in this study. Fifteen healthy age- and gen- der-matched children were also included as controls. Rou- tine urine analysis and measurement of urinary2-micro-
globulin and microalbumin levels were performed for all patients and controls. Renal-function tests, measurement of serum electrolyte, alkaline phosphatase, urinary cal- cium, blood, and urine pH levels, creation of a urinary and plasma aminogram, calculation of the glomerular filtration rate, bone radiography to detect rachitic manifestations, and abdominal ultrasound to measure renal size were per- formed for all patients.
RESULTS: Twenty-one patients had ⱖ1 renal abnor- mality. The most common was increased urinary 2-
microglobulin level (15 of 21) followed by an abnormal glomerular filtration rate, whether low or high (8 of 21), and microalbuminuria (6 of 21). Sonographically, there was nephrocalcinosis in 1 case and renal stone in an- other. The area under the receiver operating character- istic curve for2-microglobulin was 0.86 (P⫽.01) and
0.7 for the urinary microalbumin/creatinine ratio (P⫽ .15). The best cutoff level for predicting renal abnormal- ity for urinary 2-microglobulin was 0.22 mg/L with
70% sensitivity and 100% specificity, and the best cutoff value for the urinary microalbumin/creatinine ratio was 4.5 with 86% sensitivity and 50% specificity.
CONCLUSIONS: Renal abnormalities are common in patients with GSD. Urinary B2-microglobulin level can
be considered the gold standard for early detection of renal dysfunction in these patients.
LEPTIN AND LEPTIN RECEPTOR IN SERUM AND URINE FROM CHILDREN WITH
NEPHROTIC SYNDROME ACCOMPANYING HYPERLIPIDEMIA
Submitted by Xi Qiang Yang
Xi Qiang Yanga, Jian Jun Wangb, Li Jia Wanga, Qiu Lia
aChildren’s Hospital, Chongqing Medical University, Chongqing, China;bDepartment of Pediatrics, Affiliated Hospital, Northern Sichuan Medical College, Nanchong City, China
INTRODUCTION:Hyperlipidemia may cause glomer- ulosclerosis in children with nephrotic syndrome (NS).
OBJECTIVE:Our goal was to observe the role of solu- ble leptin receptor (sOBR) and leptin in serum and urine on the mechanism of hyperlipidemia in children with NS.
METHODS: Twenty-three children with untreated NS and 15 age-, gender-, and BMI-matched healthy controls were enrolled onto the study. Leptin and sOBR in serum and urine were measured by enzyme-linked immunosor- bent assay, and plasma lipid and insulin levels were de- tected by automatic biochemistry analyzer and radioim- munoassay, respectively. sOBR messenger RNA and membrane protein expression in peripheral blood mono-
nuclear cells were detected by reverse-transcription poly- merase chain reaction and immunocytochemistry.
RESULTS: Low-density lipoprotein, total cholesterol, triglyceride, and apolipoprotein A levels were increased. sOBR messenger RNA and membrane protein expres- sion by peripheral blood mononuclear cells were signif- icantly lower in the patient group compared with con- trols. The ratio of serum leptin versus sOBR (free leptin index) was significantly higher in the NS group. Urinary leptin in the patient group was higher than that in the control group. The free leptin index showed no correla- tion with BMI or total cholesterol, triglyceride, or apo- lipoprotein B levels in both groups but did show a cor- relation with plasma albumin, low-density lipoprotein, high-density lipoprotein, apolipoprotein A, and insulin levels in the patient group.
CONCLUSIONS: The reduced sOBR level, which en- hanced the biologically active form of leptin in children with NS, might be correlated partly with serum lipid parameters, albumin, and insulin. Increased free leptin in serum might be a complementary mechanism against hyperlipidemia in children with NS.
LONG-TERM PROGNOSIS OF HENOCH- SCHO¨ NLEIN NEPHRITIS IN CHILDREN Submitted by Ayse Oner
Ayse Onera,⌽zlem Erdoganb, Tuba Erenb, Gu¨lay
Demircinb, Mehmet Bu¨lbu¨lb, Sahika Baysunb,
Nilufer Ardab
aPediatric Nephrology Department, Trakya University Medicine Faculty Hospital, Edirne, Turkey;bPediatric Nephrology Department, Dr Sami Ulus Children’s Hospital, Ankara, Turkey
INTRODUCTION: The long-term prognosis in He- noch-Scho¨nlein purpura is determined principally by the development of progressive glomerulonephritis (⬎10% progress to end-stage renal failure).
OBJECTIVE:In this study we aimed to investigate the long-term prognosis of Henoch-Scho¨nlein nephritis (HSN) in childhood.
METHODS:Between 1991 and 2003, 156 patients with HSN were investigated retrospectively.
RESULTS:There were 86 boys and 70 girls with a mean age of 9.6 years. They were graded according to the degree of renal involvement: grade 1, isolated micro- scopic hematuria (n⫽31); grade 2, hematuria and mild proteinuria (n⫽60); grade 3, acute nephritic syndrome (n⫽4); grade 4, nephrotic syndrome⫾hematuria (n⫽ 18); grade 5, acute nephritic and nephrotic syndrome (n ⫽ 43). Renal biopsy was performed on 43 patients with grade 4 or 5 disease. Twenty patients had extensive crescent formation (⬎50%) as shown by the renal bi- opsy and were given triple therapy (intravenous pulse methylprednisolone [30 mg/kg per day for 3 days] fol-
lowed by oral prednisolone [OP], oral cyclophosphamide [2 mg/kg per day for 2 to 3 months], and dipyridamole). The other 23 patients with ⬍50% crescent formation were given methylprednisolone followed by OP and di- pyridamole. The patients with grade 3 or 4 disease were given OP and dipyridamole. Those with grade 1 or 2 disease were not given any immunosuppressive agent. During the follow-up period (mean: 30 ⫾3.5 months; range: 12–96 months), 23 patients with grade 1, 38 patients with grade 2, 2 patients with grade 3, 8 patients with grade 4, and 21 patients with grade 5 disease showed complete remission (59%). Of the 5 patients with extensive fibrosis shown by renal biopsy, 2 (1%) had persistent nephropathy and 3 (2%) developed end- stage renal failure. The remaining 59 patients showed near-complete recovery with minimal urinary abnor- malities (38%).
CONCLUSIONS:Although initial presentation of renal involvement determines the prognosis for those with HSN, intensive treatment with triple therapy seems to be effective for severe renal disease, especially if started before the development of fibrotic changes in crescents and tubulointerstitial tissue.